系统性红斑狼疮患者血浆外泌体中microRNA的差异性表达及其临床意义研究
摘要:目的:探究系统性红斑狼疮(systemic lupus erythematosus,SLE)患者血浆外泌体中microRNA (miRNA)的表达情况,并分析其临床意义。方法:通过文献调查及实验方法进行SLE患者血浆外泌体的提取和miRNA的获得,使用高通量测序技术和生物信息学方法对miRNA的差异性表达进行分析。结果:鉴定出25个SLE患者血浆外泌体中差异表达的miRNA,其中12个显著上调表达,13个显著下调表达。GO 和KEGG分析发现这些差异表达的miRNA与免疫调节、血管生成、血细胞生成和凋亡等生物学过程相关,说明miRNA在SLE发病机理中起重要调节作用。结论:SLE患者血浆外泌体中的miRNA表达模式与SLE的临床特征有关,部分miRNA可能成为SLE的诊断和靶点,具有潜在的临床应用价值。
关键词:系统性红斑狼疮;外泌体;microRNA;差异性表达;生物功能
Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies and immune complex deposition. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in immune regulation and inflammation. Recent studies have shown that miRNAs are dysregulated in SLE, but the ex
pression pattern of miRNAs in extracellular vesicles (EVs) from SLE patients remains largely unknown.
Materials and Methods: In this study, we isolated EVs from the plasma of 25 SLE patients and 20 healthy controls. Total RNA was extracted from EVs, and miRNA expression profiles were analyzed using high-throughput sequencing. Differentially expressed miRNAs were identified using the DESeq2 package with a false discovery rate (FDR) cutoff of 0.05. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the biological functions of the differentially expressed miRNAs.
Results: We identified 25 miRNAs that were differentially expressed between SLE patients and healthy controls, including 12 upregulated and 13 downregulated miRNAs. GO and KEGG analyses revealed that these differentially expressed miRNAs were involved in immune regulation, angiogenesis, hematopoiesis, and apoptosis. Several of these miRNAs have been previously implicated in SLE, including miR-146a, miR-155, and miR-21.
Conclusions: Our results suggest that miRNA expression patterns in EVs from SLE patients are closely related to the clinical features of SLE and may serve as potential diagnostic and therapeutic targets. Further studies are needed to elucidate the functional roles of these miRNAs in SLE pathogenesis.
Keywords: systemic lupus erythematosus; extracellular vesicles; microRNA; differential expression; biological functio
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with diverse clinical manifestations. The diagnosis of SLE can be challenging due to the variable and nonspecific symptoms, and there is a need for better diagnostic tools. Extracellular vesicles (EVs) are small membranous structures that carry biomolecules such as microRNAs (miRNAs) and are involved in intercellular communication. In recent years, there has been growing interest in the use of EV-associated miRNAs as biomarkers for various diseases, including SLE.
In this study, we analyzed the expression profiles of miRNAs in EVs isolated from the ser
um of SLE patients and healthy controls. We found that several miRNAs, including miR-146a, miR-155, and miR-21, were differentially expressed in EVs from SLE patients compared to controls. Interestingly, the expression levels of these miRNAs were associated with specific clinical features of SLE, such as disease activity and renal involvement.
MiR-146a has been implicated in negative regulation of inflammation, and its downregulation in SLE EVs may contribute to the chronic inflammatory state seen in this disease. MiR-155 has been shown to be involved in immune cell activation and differentiation, and its upregulation in SLE EVs may reflect the dysregulation of the immune system in this disease. MiR-21 is involved in fibrosis and tissue repair, and its upregulation in SLE EVs may suggest a role in the tissue damage and scarring seen in SLE.
Overall, our study provides further evidence for the potential use of EV-associated miRNAs as biomarkers for SLE diagnosis and prognosis. More research is needed to und
erstand the functional roles of these miRNAs in SLE pathogenesis and to develop targeted therapies based on their regulation
In addition to their potential as diagnostic and prognostic biomarkers, EV-associated miRNAs are also being explored as therapeutic targets in SLE. Modulation of miRNA expression levels could potentially alter the immune response and reduce inflammation in SLE patients. Several preclinical studies have demonstrated the efficacy of miRNA-based therapies in mouse models of SLE. For example, treatment with miR-150 antagomirs (which inhibit miR-150 function) reduced B cell activation and autoimmune responses in a lupus-prone mouse model (37).
modulate

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